Big Pharma Attempts to Extend Own Lifespan by Activating Sirtuins

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Can drugs that supposedly “activate” a controversial target—sirtuin proteins—stop or even reverse the aging process? A new report this week said “No.” According to this report, published Wednesday night in Nature, sirtuin activators do not extend lifespan in roundworms and flies and earlier studies that said they did were flawed. Nonetheless, GlaxoSmithKline (GSK) continues to invest hundreds of millions of dollars into developing drugs to hit these targets—more about their findings below—and if the drugs work, for whatever reason, the scientific squabbles will not matter.

I recently had the chance to hear Harvard professor David Sinclair talk publicly about his and GSK’s research into sirtuin activators. Sinclair was the scientific founder of Sirtris and he reported at a forum on longevity in Cambridge, MA, that GSK has high hopes of near-term confirmation in mice that some sirtuin activators do extend lifespan. Based on its continued investment, GSK still believes that the $720 million acquisition of Sirtris in 2008 was a smart one.

The Nature report, just the latest in a series of publications that question the sirtuin-longevity link, will be even tougher for Sinclair and other sirtuin researchers to overcome. The new research reported that sirtuin proteins, when overexpressed in nematode worms and fruit flies, do not actually have an effect on longevity. This directly contradicts the original publications linking Sir2 and other sirtuins with increased lifespan. The new report further goes on to contradict the landmark 2006 paper, also published in Nature, in which Harvard researchers led by Sinclair reported that mice fed resveratrol which, they demonstrated using expression analysis, activated sirtuins, live on average 20 percent longer and in some cases much longer than that.

The same researchers, both at University College London, went on the record as sirtuin skeptics in 2007. David Gems and Linda Partridge then set out to prove their claim that the original sirtuin and resveratrol findings, which led to the founding and eventual acquisition of Sirtris, were irreparably flawed. Building on earlier reports that the round worms used in the original studies carried a gene that control organisms did not carry, and that it was this gene that predisposed the worms to live longer, Gems and Partridge showed in this paper that organisms identical to one another except for the expression level of sirtuins could not be made to live longer.

Sirtuin research is nothing if not contentious. Apparently eager to fan the flames, Nature in the same issue this week published a rebuttal from Leonard Guarente, the author … Next Page »

A few points that almost everyone is missing in their analysis of this study. Transmax resveratrol reply.

1. This is one study, which only addressed the Sirtuins, and only from the standpoint of longevity. It is an extremely narrowly focused and did not involve any actual experimentation. The non-scientific press is again jumping to a conclusion that is not supported by the data and findings of the study.
3. The benefits of resveratrol are in its ability to extend the period of healthy lifespan, not necessarily to directly extend lifespan per se. However, if resveratrol prevents one from developing diabetes, heart disease or a cancerous tumor it certainly has extended the life and healt span of that individual.
4. There are over 5,000 published peer-reviewed studies on resveratrol, as well as the principal analogs of resveratrol, which elucidate the stilbenes ’chemo protective properties with respect to the so-called diseases of aging and obesity, including type 2 diabetes, coronary artery disease, cancer, neurological conditions and dysfunction, inflammatory conditions such as arthritis and other autoimmune conditions, physical fitness, endurance and mitochondrial function and density, and many others.
5. Resveratrol operates via multiple clearly identified pathways apart from sirtuin modulation. These include Nf Kappa B, Cox 2, P-53, pro apoptiic and autophagy activation and regulation, mTOR, FOX0, and over 100 others
6. As the other sturcturally related molecules to resverarol, such as pterostilbene and polydatin are studied and analyzed additional beneficial effects are being confirmed.
7. In the limited number of human clinical trials, mostly with transmax resveratrol, either underway or recently completed the health span extension and disease prevention properties are confirmed.
8. The issue of longevity is extremely complicated. There is probably no gene or set of genes that directly promote or inhibit longevity. Natural selection for longevity is not in the interest of the survival of any species, with the possible exception of humans. Nature is ambivalent when it comes to longevity past the individual’s age of reproduction.

Burak Kutlu

“The non-scientific press is again jumping to a conclusion that is not supported by the data and findings of the study”. I think a disclosure of COI is warranted here.